Study of ITER equatorial port plug handling system and vacuum sealing interface

In the field of the ITER port plug engineering and integration task, CEA has contributed to define proposals concerning the port plugs vacuum sealing interface with the vessel flange and the equatorial plug handling.The 2001 baseline vacuum flange sealing consisted of TIG welding of a 316L strip plate on to U shapes. This arrangement presented some issues like welding access, implementation of tools, lip consumption, complex local leak test, continuous leak checking. Therefore, an alternate sealing solution based on the use of metallic gaskets is proposed. The different technical aspects are discussed to explain how this design can simplify the maintenance and deal with safety and vacuum requirements.The design of the mechanical attachment and vacuum sealing of the plug has constantly evolved, but the associated remote handling equipment was not systematically reviewed. An update of the cask and maintenance procedure was studied in order to design it in accordance with the last generic plug flange design. This includes a concept of a gripping system that uses the plug flange bolting area and, to help the remote handling process, a cantilever assisting system is suggested to increase the reliability of the transfer operation between vacuum vessel and cask.     

Molecular Mechanisms and Physiological Changes behind Benign Tracheal and Subglottic Stenosis in Adults

Laryngotracheal stenosis (LTS) is a complex and heterogeneous disease whose pathogenesis remains unclear. LTS is considered to be the result of aberrant wound-healing process that leads to fibrotic scarring, originating from different aetiology. Although iatrogenic aetiology is the main cause of subglottic or tracheal stenosis, also autoimmune and infectious diseases may be involved in causing LTS. Furthermore, fibrotic obstruction in the anatomic region under the glottis can also be diagnosed without apparent aetiology after a comprehensive workup; in this case, the pathological process is called idiopathic subglottic stenosis (iSGS). So far, the laryngotracheal scar resulting from airway injury due to different diseases was considered as inert tissue requiring surgical removal to restore airway patency. However, this assumption has recently been revised by regarding the tracheal scarring process as a fibroinflammatory event due to immunological alteration, similar to other fibrotic diseases. Recent acquisitions suggest that different factors, such as growth factors, cytokines, altered fibroblast function and genetic susceptibility, can all interact in a complex way leading to aberrant and fibrotic wound healing after an insult that acts as a trigger. However, also physiological derangement due to LTS could play a role in promoting dysregulated response to laryngo-tracheal mucosal injury, through biomechanical stress and mechanotransduction activation. The aim of this narrative review is to present the state-of-the-art knowledge regarding molecular mechanisms, as well as mechanical and physio-pathological features behind LTS.     

Pathogenetic Mechanisms of Hypertension–Brain-Induced Complications: Focus on Molecular Mediators

There is growing evidence that hypertension is the most important vascular risk factor for the development and progression of cardiovascular and cerebrovascular diseases. The brain is an early target of hypertension-induced organ damage and may manifest as stroke, subclinical cerebrovascular abnormalities and cognitive decline. The pathophysiological mechanisms of these harmful effects remain to be completely clarified. Hypertension is well known to alter the structure and function of cerebral blood vessels not only through its haemodynamics effects but also for its relationships with endothelial dysfunction, oxidative stress and inflammation. In the last several years, new possible mechanisms have been suggested to recognize the molecular basis of these pathological events. Accordingly, this review summarizes the factors involved in hypertension-induced brain complications, such as haemodynamic factors, endothelial dysfunction and oxidative stress, inflammation and intervention of innate immune system, with particular regard to the role of Toll-like receptors that have to be considered dominant components of the innate immune system. The complete definition of their prognostic role in the development and progression of hypertensive brain damage will be of great help in the identification of new markers of vascular damage and the implementation of innovative targeted therapeutic strategies.     

Porcine Small Intestinal Submucosa (SIS) as a Suitable Scaffold for the Creation of a Tissue-Engineered Urinary Conduit: Decellularization,Biomechanical and Biocompatibility Characterization Using New Approaches

Bladder cancer (BC) is among the most common malignancies in the world and a relevant cause of cancer mortality. BC is one of the most frequent causes for bladder removal through radical cystectomy, the gold-standard treatment for localized muscle-invasive and some cases of high-risk, non-muscle-invasive bladder cancer. In order to restore urinary functionality, an autologous intestinal segment has to be used to create a urinary diversion. However, several complications are associated with bowel-tract removal, affecting patients’ quality of life. The present study project aims to develop a bio-engineered material to simplify this surgical procedure, avoiding related surgical complications and improving patients’ quality of life. The main novelty of such a therapeutic approach is the decellularization of a porcine small intestinal submucosa (SIS) conduit to replace the autologous intestinal segment currently used as urinary diversion after radical cystectomy, while avoiding an immune rejection. Here, we performed a preliminary evaluation of this acellular product by developing a novel decellularization process based on an environmentally friendly, mild detergent, i.e., Tergitol, to replace the recently declared toxic Triton X-100. Treatment efficacy was evaluated through histology, DNA, hydroxyproline and elastin quantification, mechanical and insufflation tests, two-photon microscopy, FTIR analysis, and cytocompatibility tests. The optimized decellularization protocol is effective in removing cells, including DNA content, from the porcine SIS, while preserving the integrity of the extracellular matrix despite an increase in stiffness. An effective sterilization protocol was found, and cytocompatibility of treated SIS was demonstrated from day 1 to day 7, during which human fibroblasts were able to increase in number and strongly organize along tissue fibres. Taken together, this in vitro study suggests that SIS is a suitable candidate for use in urinary diversions in place of autologous intestinal segments, considering the optimal results of decellularization and cell proliferation. Further efforts should be undertaken in order to improve SIS conduit patency and impermeability to realize a future viable substitute.     

A Modular Composite Device of Poly(Ethylene Oxide)/Poly(Butylene Terephthalate) (PEOT/PBT) Nanofibers and Gelatin as a Dual Drug Delivery System for Local Therapy of Soft Tissue Tumors

In the clinical management of solid tumors, the possibility to successfully couple the regeneration of injured tissues with the elimination of residual tumor cells left after surgery could open doors to new therapeutic strategies. In this work, we present a composite hydrogel–electrospun nanofiber scaffold, showing a modular architecture for the delivery of two pharmaceutics with distinct release profiles, that is potentially suitable for local therapy and post-surgical treatment of solid soft tumors. The composite was obtained by coupling gelatin hydrogels to poly(ethylene oxide)/poly(butylene terephthalate) block copolymer nanofibers. Results of the scaffolds’ characterization, together with the analysis of gelatin and drug release kinetics, displayed the possibility to modulate the device architecture to control the release kinetics of the drugs, also providing evidence of their activity. In vitro analyses were also performed using a human epithelioid sarcoma cell line. Furthermore, publicly available expression datasets were interrogated. Confocal imaging showcased the nontoxicity of these devices in vitro. ELISA assays confirmed a modulation of IL-10 inflammation-related cytokine supporting the role of this device in tissue repair. In silico analysis confirmed the role of IL-10 in solid tumors including 262 patients affected by sarcoma as a negative prognostic marker for overall survival. In conclusion, the developed modular composite device may provide a key-enabling technology for the treatment of soft tissue sarcoma.     

Explicit versus implicit method for radiative heat transfer in gray and diffuse enclosures

The paper presents an explicit formulation of the radiative problem in gray enclosures. The method is based on a series expansion that derives the mutual radiation factors by means of summation of the contributions to the radiative thermal exchange given by the multi-reflection process. A mathematical proof that the infinite expansion converges to the well known solution, given by the implicit formulation and based on radiosities balance, is provided. Moreover a parametric analysis of the approximation induced by the explicit algorithm, as a result of the truncation order in the calculation of the series expansion, is carried out. The analysis shows how the precision of every approximation order is mainly related to the surface averaged infrared reflectance and is weakly dependent on the reflectance distribution. For high emissive and low reflecting surfaces, very few summations are required to meet high precision; the same level of precision is achievable also with medium and high reflecting surfaces, by increasing the truncation order of the series. More generally, the explicit formulation provides an alternative approach to problems involving multi-reflecting cavities in different engineering applications, from heat transfer to optics.     

The structure of toluene-doped counterflow gaseous diffusion flames

The structure of gaseous counterflow diffusion flames perturbed with the addition of hundreds of ppm of prevaporized toluene is studied in two distinct flame environments: a blue methane flame stabilized on the fuel side of the gas stagnation plane and an incipiently sooting ethylene flame stabilized on the oxidizer side. The goal is to provide a well-defined testbed in terms of temperature–time history, major species and part of the radical pool, for the examination of reference fuels that are critical components of practical fuel blends. Gas samples are extracted from the flame with fused silica microprobes for subsequent GC/MS analysis and thermocouples and thin filament pyrometry are used to characterize the temperature field. Profiles of critical toluene pyrolysis products and stable soot precursors are compared with computational models using two semi-detailed chemical mechanisms. Results show that in the methane flame some oxygen containing radicals like O and OH are contributing early on to the toluene destruction path. In the incipiently sooting ethylene flame, the primary attack is from H alone. This finding confirms the different challenges that such flames pose to the validation of a chemical kinetic mechanism. The onset of toluene decay in these flames begins at relatively modest temperatures, on the order of 800 K. This reactivity is captured reasonably well by both chemical mechanisms in the methane flame, in the absence of reactants larger than C2, but not so in the ethylene flame, in the presence of a richer, more complex mixture. The aromatic ring opening mechanisms are not adequately modeled in either case. This discrepancy has implications for the modeling of practically relevant fuel blends with both aliphatic and aromatic compounds. The dominant species larger than toluene in the doped methane flame is ethylbenzene, which at least one of the mechanisms reproduces quite well. The largest measured species in the incipiently sooting flame is indene, whose concentration increase due to toluene addition is properly captured by one of the models. The experimental dataset reported here may help identifying future improvements to chemical kinetic mechanisms and complement other reactor datasets lacking the coupling of kinetics and transport of flame environments.     

A Comparison Between the Interpolated Bounce-Back Scheme and the Immersed Boundary Method to Treat Solid Boundary Conditions for Laminar Flows in the Lattice Boltzmann Framework

In this paper, the interpolated bounce-back scheme and the immersed boundary method are compared in order to handle solid boundary conditions in the lattice Boltzmann method. These two approaches are numerically investigated in two test cases: a rigid fixed cylinder invested by an incoming viscous fluid and an oscillating cylinder in a calm viscous fluid. Findings in terms of velocity profiles in several cross sections are shown. Differences and similarities between the two methods are discussed, by emphasizing pros and cons in terms of stability and computational effort of the numerical algorithm.     

Semi-quantitative monitoring of confluence of adherent mesenchymal stromal cells on calcium-phosphate granules by using widefield microscopy images

The analysis of cell confluence and proliferation is essential to design biomaterials and scaffolds to use as bone substitutes in clinical applications. Accordingly, several approaches have been proposed in the literature to estimate the area of the scaffold covered by cells. Nevertheless, most of the approaches rely on sophisticated equipment not employed for routine analyses, while the rest of them usually do not provide significant statistics about the cell distribution. This research aims at studying confluence and proliferation of mesenchymal stromal cells (MSC) adherent on OSPROLIFE^®, a commercial biomaterial in the form of granules. In particular, we propose a Computer Vision approach that can routinely be employed to monitor the surface of the single granules covered by cells because only a standard widefield fluorescent microscope is required. In order to acquire significant statistics data, we analyse wide-area images built by using MicroMos v2.0, an updated version of a previously published software specific for stitching brightfield and phase-contrast images manually acquired via a widefield microscope. In particular, MicroMos v2.0 permits to build accurate “mosaics” of fluorescent images, after correcting vignetting and photo-bleaching effects, providing a consistent representation of a sample region containing numerous granules. Then, our method allows to make automatically a statistically significant estimate of the percentage of the area of the single granules covered by cells. Finally, by analysing hundreds of granules at different time intervals we also obtained reliable data regarding cell proliferation, confirming that not only MSC adhere onto the OSPROLIFE^® granules, but even proliferate over time.